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Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

20 Participants Needed

Leniolisib for Common Variable Immunodeficiency

Overseen ByDerrick Carter

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Pharming Technologies B.V.

Must not be taking: Immunosuppressants, mTOR inhibitors

Disqualifiers: T cell deficiency, NK cell deficiency, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must not have used immunosuppressive medications like mTOR or PI3K inhibitors within 3 weeks, or B cell depleting antibodies like rituximab within 6 months. Some medications like abatacept and enteral budesonide are allowed if you've been on a stable dose for over 3 months.

How does the drug leniolisib differ from other treatments for common variable immunodeficiency?

Leniolisib is unique because it is an oral drug that specifically targets the PI3Kδ pathway, which is crucial for immune cell function, and has shown efficacy and tolerability in treating similar immune disorders like activated PI3Kδ syndrome. Unlike other treatments, it selectively inhibits the δ isoform without causing severe immune-related side effects.¹ ² ³ ⁴ ⁵

What is the purpose of this trial?

In this study, common variable immunodeficiency (CVID) patients will all receive the study drug, leniolisib, for a treatment period of 6 months. Participants will start on a lower dose of leniolisib, followed by a mid and then a higher dose level. The primary goal is to assess the safety and tolerability of leniolisib, and secondary goal is to assess the potential for leniolisib to provide benefits for patients.

Eligibility Criteria

This trial is for people aged 12-75 with common variable immunodeficiency (CVID). They should have low immune protein levels, no secondary causes of the condition, specific genetic markers if present, and signs of lymphoproliferation. Participants must also experience symptoms like chronic pain or blood cell count issues related to CVID.

Inclusion Criteria

I have been diagnosed with CVID due to low IgG levels.

At screening, vital signs ranges must meet specified criteria

I am between 12 and 75 years old.

See 3 more

Exclusion Criteria

I am taking medication that affects the CYP3A enzyme.

Positive blood PCR for cytomegalovirus or adenovirus

I have a history of infections indicating a significant immune deficiency.

See 19 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leniolisib with dose escalation: 10 mg BID for 4 weeks, 30 mg BID for 4 weeks, and 70 mg BID for 16 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

Leniolisib

Trial Overview The study tests leniolisib in CVID patients over a 6-month period. It starts with a lower dose that increases to mid and higher levels. The main aim is to check how safe it is and how well participants tolerate it; the second aim is to see if it helps improve their health.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: LeniolisibExperimental Treatment1 Intervention

All subjects participating will receive leniolisib film-coated tablets (FCTs) with a planned dose regimen consisting of a starting dose of 10 mg twice daily (BID) for 4 weeks, followed by a dose escalation to 30 mg BID for 4 weeks, and then 70 mg BID for an additional 16 weeks.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Pharming Technologies B.V.

Lead Sponsor

Trials

Recruited

1,400+

Lahey Hospital & Medical Center

Collaborator

Trials

Recruited

3,100+

Findings from Research

Leniolisib is the only PI3Kδ inhibitor that has demonstrated both efficacy and tolerability for treating activated phosphoinositide 3-kinase δ syndrome (APDS), a genetic condition affecting immune function.

Unlike other PI3Kδ inhibitors that can cause severe side effects like colitis and neutropenia, leniolisib selectively targets the δ isoform without affecting the δ or γ isoforms, making it a safer option for patients with APDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond.Cant, AJ., Chandra, A., Munro, E., et al.[2023]

Leniolisib (JOENJA®) is an oral medication that selectively inhibits the PI3Kδ enzyme and has been approved for treating activated PI3Kδ syndrome (APDS) in patients aged 12 and older, marking a significant advancement in immunodeficiency treatment.

The drug is currently under review in the European Union for the same indication, although its development for Sjögren's syndrome has been discontinued.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leniolisib: First Approval.Duggan, S., Al-Salama, ZT.[2023]

In a phase 3 trial involving 31 patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS), the oral drug leniolisib significantly reduced lymph node size and increased the percentage of naïve B cells, indicating improved immune function.

Leniolisib was well tolerated, with fewer treatment-related adverse events reported compared to placebo, suggesting it is a safe and effective option for managing immune dysregulation in APDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome.Rao, VK., Webster, S., Šedivá, A., et al.[2023]